University of Dundee

"Scratching the surface: Biogenesis and function of the C. difficile surface layer"

Event Date: 
Thursday, May 5, 2016 - 10:00
Event Location: 
MSI Small Lecture Theatre
Host: 
Professor Nicola Stanley-Wall FRSE FRSB FEAM
Event Speaker: 
Dr Robert Fagan
Institution: 
University of Sheffield
Event Type: 
Seminar
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Clostridium difficile is the leading cause of antibiotic-associated diarrhoea, causing significant morbidity and mortality. C. difficile produces a paracrystalline 2D array of proteins (S-layer) that completely coats the bacterial surface. The S-layer consists of approx. 500,000 copies of the SlpA protein and is functionalised by an additional 28 related cell wall proteins. Producing the S-layer requires a significant metabolic effort by the bacterium but little is known about its function as the encoding gene, slpA, is essential. In recent years we have identified a dedicated secretion pathway and a number of accessory proteins that are required for assembly of the S-layer. Using 2D electron diffraction we have also begun to build a picture of the C. difficile  cell surface. Despite these new insights, functional analysis has been hampered by a lack of isogenic slpA mutants. In collaboration with AvidBiotics (South San Francisco) we have recently isolated a spontaneous slpA mutant that has allowed genetic manipulation of the S-layer for the first time. Using this new tool we have identified pleiotropic functions for the S-layer including resistance to immune effectors and antibiotics, cell wall biogenesis and sporulation.